The Mind Research Network, 1101 Yale Blvd. NE, Albuquerque, NM, 87106, USA.
Nene and Jamie Koch Comprehensive Movement Disorder Center, Department of Neurology, The University of New Mexico, Albuquerque, NM, 87131, USA.
J Neurol. 2023 Feb;270(2):746-758. doi: 10.1007/s00415-022-11461-9. Epub 2022 Nov 10.
Lewy body diseases, such as Parkinson's disease and dementia with Lewy bodies, vary in their clinical phenotype but exhibit the same defining pathological feature, α-synuclein aggregation. Microbiome-gut-brain dysfunction may play a role in the initiation or progression of disease processes, though there are multiple potential mechanisms. We discuss the need to evaluate gastrointestinal mechanisms of pathogenesis across Lewy body diseases, as disease mechanisms likely span across diagnostic categories and a 'body first' clinical syndrome may better account for the heterogeneity of clinical presentations across the disorders. We discuss two primary hypotheses that suggest that either α-synuclein aggregation occurs in the gut and spreads in a prion-like fashion to the brain or systemic inflammatory processes driven by gastrointestinal dysfunction contribute to the pathophysiology of Lewy body diseases. Both of these hypotheses posit that dysbiosis and intestinal permeability are key mechanisms and potential treatment targets. Ultimately, this work can identify early interventions targeting initial disease pathogenic processes before the development of overt motor and cognitive symptoms.
路易体病，如帕金森病和路易体痴呆，在其临床表型上存在差异，但表现出相同的明确病理特征，即α-突触核蛋白聚集。微生物组-肠道-大脑功能障碍可能在疾病过程的开始或进展中发挥作用，尽管存在多种潜在机制。我们讨论了评估路易体病中胃肠道发病机制的必要性，因为疾病机制可能跨越诊断类别，并且“身体首先”的临床综合征可能更好地解释了这些疾病在临床表现上的异质性。我们讨论了两个主要假设，即α-突触核蛋白聚集发生在肠道中，并以类朊病毒样方式传播到大脑，或者由胃肠道功能障碍驱动的系统性炎症过程导致路易体病的病理生理学。这两个假设都假设肠道菌群失调和肠道通透性是关键机制和潜在的治疗靶点。最终，这项工作可以确定在出现明显的运动和认知症状之前，针对初始疾病发病机制的早期干预措施。
